The Clinical and Translational Research Award (CTSA) has been greeted enthusiastically by the University of Pennsylvania (Penn), A strategic plan had identified clinical and translational research as a priority, leading to formation of the Institute for Translational Medicine and Therapeutics (ITMAT) in January 2005. ITMAT anticipated some aspects of the CTSA - inclusion of the GCRC, dedicated "dry" and "wet bench" space for translational research and a robust educational program, configured on a Masters in Translational Research (MTR). This CTSA proposal prompted intra and inter-institutional consideration of how to build on this achievement. This has forged a transformational alliance between Penn, the Children's Hospital of Philadelphia (CHOP), the Wistar Institute (Wl) and the University of the Sciences in Philadelphia (USP). Faculty from 9 of the 12 schools at Penn and from the partner institutions are represented in leadership roles in the response to this CTSA. ITMAT, designated as the "academic home" for clinical and translational research, has been broadened to serve a trans-institutional role. Its structure has been transformed to foster interdisciplinary science from discovery of new molecules through to the study of drug action in large populations. This has been accomplished by developing interdisciplinary centers, related cores, innovative interdisciplinary programs of research and strategies to engage and inform communities and their physicians. A particular emphasis has been placed on training and innovative programs, which cover the entire career span, engaging undergraduate students through to mature clinicians, are proposed. These include the flexible use of the MTR and new tracks in the Masters in Clinical Epidemiology (MSCE) with the MD, PhD, VMD, MSN, DMD and MBA degrees; the set aside of places for medical school entrants pursuing MD-MTR/MSCE degrees and the flexible use of our diverse faculty tracks at Penn and CHOP to broaden physician engagement in research. These initiatives will be pursued in partnership with industry (e.g. GSK, Oracle), the State of Pennsylvania (BioAdvance), the FDA and a national network of institutions holding CTSAs.An elaborate and diversified approach to tracking the productivity of this program has been developed and will be integrated into a national plan with similar centers. In summary, this initiative has fostered (i) an integrated strategy to clinical and translational research by Penn, CHOP, the Wl and USP and (ii) the transformation of ITMAT. This will permit the development of interdisciplinary structures designed, to foster and facilitate research and education in this emerging discipline.